The invention relates to “active implantable medical devices” as defined by the Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities.
It more specifically relates to devices that deliver pacing therapies of the nervous system, including vagus nerve stimulation (“VNS”). This type of stimulation may be referred to generally as “neurostimulation”. The device includes for this purpose a lead with an electrode implanted on the vagus nerve and a generator delivering VNS pulses on this electrode.
Central nervous system stimulation therapy is recognized with respect to many disorders, such as epilepsy, pain, heart failure, apnea, obesity, etc. For the treatment of disorders such as heart failure, epilepsy or obesity, the devices typically include a lead with an electrode implanted on the vagus nerve (called “VNS lead”) and a generator supplying VNS pulses on this electrode.
In some therapies, the VNS stimulation profile is composed of repetitive bursts or pulse trains produced during periods of “activity” or “ON periods” of a few tens of seconds, interspersed with periods of “inactivity” or “OFF periods” of a few minutes during which stimulation is no longer issued.
The vagus nerve may be stimulated synchronously with the heart rate, in which case the device includes methods for collecting myocardium depolarization waves, typical methods for collecting an ECG by a subcutaneous electrode, or an EGM by an electrode implanted on or in the myocardium.
The VNS stimulation is particularly well suited to the treatment of cardiac disorders, especially in patients at risk of heart failure, wherein the vagus nerve stimulation acts on cardiovascular functions by reducing the heart rate. This reduces the cardiac contractility and increases the duration of diastole, which may help reduce the development of cardiac remodeling which may lead to a worsening heart failure status.
Indeed, in a patient with heart failure, or in the post-myocardial infarction, sympathetic activity is excessive (hypertonic sympathetic state), with a rather depressed parasympathetic system, leading to a heart rate faster than normal.
The problem addressed by the invention is related to the fact that the efficiency of neuronal therapy by VNS stimulation, if it is effective at the beginning of its implementation, decreases rapidly, probably due to compensation phenomena coming from the formation of a physiological control loop.
Thus, if, for example, the heart rate (or RR interval) of the patient is measured just before and just after the triggering of the VNS stimulation (that is to say just before and just after the transition from OFF to ON), there is a significant decrease in heart rate, which reaches a maximum after about ten seconds. However, all things being equal, the frequency starts to gradually increase even as the VNS stimulation continues to be applied. After a few tens of seconds, slower heart beat obtained by the stimulation VNS is only from 80% to 60% of what it was originally (when the VNS stimulation had begun to be applied). However, if the VNS stimulation is stopped (transition from ON to OFF) then reactivated later (end of OFF period), the initial effectiveness is recovered, followed by the same gradual weakening of the effect of the therapy.
The continuous application of VNS stimulation is therefore of diminishing benefit and it is for this reason that the technique of ON and OFF alternating periods of stimulation is implemented.
Another aspect to be considered is that of deleterious events such as cough, apnea, ectopic ventricular contractions, or PVCs (Premature Ventricular Contractions), which may occur as secondary effects of VNS stimulation. If such symptoms occur, the VNS stimulation should be reduced so that the drawbacks of the latter do not outweigh the benefits.
Today, the durations of the ON and OFF periods are essentially empirically programmed by the practitioner. The practitioner must find a compromise between a sufficiently long ON period for the VNS stimulation is beneficial to the patient, while avoiding a prolonged stimulation does not produce deleterious effects such as the occurrence of cough, etc. In practice, the practitioner should follow patients over a long period so as to finely adjust the durations of ON and OFF periods to the best of each patient.
Procedures that could help practitioners program these parameters would be beneficial, particularly in the field of cardiac rhythm management, especially for patients experiencing heart failure. As explained above, the ON duration periods have a significant impact on changes in rhythmic and/or hemodynamic parameters.